A Study to Assess the Effects of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine

An Open-Label, Single-Dose, Parallel-Group Study to Assess the Effects of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine

The purpose of this study is to evaluate the pharmacokinetics, safety, and tolerability of intranasally administered esketamine in both participants with varying stages of hepatic impairment and healthy participants.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment; Normal Hepatic Function
• Intervention / Treatment: Drug: Esketamine

Detailed Description

This is a parallel group, single-center, single-dose, open-label (all people know the identity of the intervention), study to assess the pharmacokinetics and safety of a single 28 milligram (mg) dose of esketamine in both participants with varying stages of hepatic impairment and healthy participants. The participants will be assigned to 1 of 3 groups (8 participants per group) based on hepatic impairment which will be classified during Screening. Cohort 1 (participants with moderate hepatic impairment), Cohort 2 (participants with mild hepatic impairment), and Cohort 3 (participants with normal hepatic function and no evidence of liver damage). Participants will self-administer a single dose of intranasal Esketamine 28 mg. The total duration of the study from Screening through Follow-up, is approximately 34 to 38 days. Blood and urine samples for assessment of Esketamine pharmacokinetics will be collected for up to 60 hours after study drug administration. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Cohorts 1, 2 and 3 (All participants):

• Body mass index (BMI) between 18 and 34 kilogram (kg)/meter square ([m]^2) (inclusive), and body weight not less than 50 kilogram (kg)
• Creatinine clearance of greater than or equal to (> =) 60 milliliter per minute (mL/min) based on the Cockcroft-Gault equation
• Signed an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study

Cohorts 1 and 2 (Participants with Hepatic impairment):

• A total Child-Pugh score of 5 or 6 for participants with mild impairment and between 7 and 9 (inclusive) for participants with moderate impairment
• Participants must have stable hepatic function and consistent classification (mild or moderate hepatic impairment) between Screening and Day -1

Exclusion Criteria:

Cohorts 1, 2 and 3 (All participants):

• Participants of Asian origin
• Diagnosed with a current or previous psychotic or major depressive disorder (MDD) with psychosis, bipolar or related disorder, intellectual disability, borderline personality disorder, or antisocial personality disorder

Cohorts 1 and 2 (Participants with Hepatic impairment):

• History of hepatopulmonary syndrome, hydrothorax or hepatorenal syndrome
• Positive test for alcohol or drugs of abuse per local standard practices

Cohorts 3 (Healthy participants):

• Clinically significant medical illness
• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at Screening or at admission to the study center (Day -1) as deemed appropriate by the investigator
• Positive test for human immunodeficiency virus (HIV) 1 and 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C antibodies at Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants with moderate hepatic impairment will receive esketamine solution (containing 14 milligram [mg] of esketamine base per 100 microliter [mcl]) by intranasal route into each nostril using nasal spray pump at 0 hour (h) on Day 1.	Drug: Esketamine; Esketamine 28 mg will be self-administered by participants as intranasal spray at 0 hour (h) on Day 1.; Other Names: JNJ-54135419
Experimental: Cohort 2; Participants with mild hepatic impairment will receive esketamine solution (containing 14 mg of esketamine base per 100 mcl) by intranasal route into each nostril using nasal spray pump at 0h on Day 1.	Drug: Esketamine; Esketamine 28 mg will be self-administered by participants as intranasal spray at 0 hour (h) on Day 1.; Other Names: JNJ-54135419
Experimental: Cohort 3; Participants with normal hepatic function and no evidence of liver damage will receive esketamine solution (containing 14 mg of esketamine base per 100 mcl) by intranasal route into each nostril using nasal spray pump at 0h on Day 1.	Drug: Esketamine; Esketamine 28 mg will be self-administered by participants as intranasal spray at 0 hour (h) on Day 1.; Other Names: JNJ-54135419

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax)	The Cmax is the maximum plasma concentration.	up to 60 hours after study drug administration
Time to Reach Maximum Concentration (tmax)	Time to reach the maximum observed plasma concentration.	up to 60 hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to Last (AUC [0-last])	The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.	up to 60 hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.	up to 60 hours after study drug administration
Elimination Half-life period (t1/2) Associated with the Terminal Slope (Lambda z)	Elimination half-life associated with the terminal slope (lambda[z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).	up to 60 hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to 12 Hours (AUC [0-12])	The AUC (0-12) is the area under the plasma concentration-time curve from time 0 to 12 hours post-dose.	up to 12 hours after study drug administration
Rate Constant (Lambda[z])	Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.	up to 60 hours after study drug administration
Cmax Metabolite to Parent Ratio (MPR Cmax)	Cmax metabolite to parent ratio, and corrected for molecular weight if necessary.	up to 60 hours after study drug administration
AUC(last) Metabolite to Parent Ratio (MPR AUC[last])	AUC(last) metabolite to parent ratio, and corrected for molecular weight if necessary.	up to 60 hours after study drug administration
AUC (infinity) Metabolite to Parent Ratio (MPR AUC [infinity])	AUC (infinity) metabolite to parent ratio, and corrected for molecular weight if necessary.	up to 60 hours after study drug administration
Amount of Drug Excreted in Urine (Ae)	Total amount excreted into the urine, calculated as the sum of all Ae(t1-t2) intervals.	up to 60 hours after study drug administration
Percentage of Drug dose Excreted into Urine	Total amount excreted into the urine, expressed as a percentage of the administered dose, calculated as (Ae/dose)*100, and corrected for molecular weight if necessary.	up to 60 hours after study drug administration
Renal Clearance	Renal clearance calculated as Ae/AUC (infinity).	up to 60 hours after study drug administration
Ae Metabolite to Parent Ratio (MPR Ae)	Ae metabolite to parent ratio, and corrected for molecular weight if necessary.	up to 60 hours after study drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Baseline up to Day 11

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2015
• Primary Completion (Actual): February 27, 2017
• Study Completion (Actual): February 27, 2017

Study Registration Dates

• First Submitted: November 19, 2015
• First Submitted That Met QC Criteria: November 19, 2015
• First Posted (Estimated): November 20, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Healthy; Pharmacokinetics; Hepatic Impairment; Esketamine
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: CR108098; ESKETINTRD1011 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No